We propose to purchase a highly sensitive and selective LC/MS/MS system in support of development of new and established markers for exposure and health studies. The high sensitivity and selectivity are needed for many applications such as the new generation of low-flow air monitors and to identify trace biomarkers in volume-constrained biological samples, is a primary justification of the need for this instrument. The ability to do this while increasing sample throughput (decreasing backlogs) and potentially lowering costs significantly will be a major benefit to all facility users. Many health studies only have access to smaller and smaller volumes of the biological sample of interest, such as dried blood spots from the state birth record or exhaled breath condensate, in which biomarkers from lung fluid has been diluted for more than 100 times. Measuring various biomarkers in these samples requires instruments that are able to minimize the matrix interference while having better sensitivity than those bought just a few years ago. Similarly, trace organic pollutants measured in samples collected by a new generation of miniaturized low-flow rate air monitors provide analytical challenges both in sensitivity and selectivity. These samplers have been developed to better characterize individual and population exposures to fine particulate matter (PM2.5) and its associated pollutants. However, the miniaturization and low noise design leads to low flow rates, which in turn collect 1 to 10% of the mass collected by traditional samplers. As such there is an emerging need for much more sensitive instruments so that measurements of target organic compounds can be made on the samples. The proposed system comprises the AB Sciex Qtrap 6500 mass spectrometer and a Shimadzu NEXERA X2 ultra high-performance liquid chromatography. The proposed system provides an unprecedented level of sensitivity and selectivity, while being a versatile instrument that would meet our analytical requirements. The Qtrap 6500 would be a major upgrade, replacing our 15 year old, degraded Thermo TSQ Quantum Classic LC/MS/MS and supporting the needs of an active user group, which we expect to grow with time due to the high sensitivity and high throughput capabilities and relatively low analytical fees. The instrument will be hosted in a stat of the art, HEPA filtered laboratory and strong institutional commitment has been made by two units of Columbia University to ensure the facility's success in the first five years and can be extended to later years, if necessary. Additional resources are expected for method development in the LC/MS/MS core laboratory via the Columbia P30 NIEHS Center calls for pilot project proposals.